Methods for generating chlorine dioxide and compositions for disinfecting

ABSTRACT

A method for generating chlorine dioxide which involves contacting a stable precursor with a transition metal in a buffered aqueous medium.

This application is a division of application Ser. No. 969,549, filedOct. 30, 1992, now U.S. Pat. No. 5,246,662, which is a continuation ofapplication Ser. No. 765,219, filed Sep. 24, 1991, now abandoned, whichis a division of application Ser. No. 416,074 filed Oct. 2, 1989, nowU.S. Pat. No. 5,078,908.

SCOPE OF THE INVENTION

This invention relates to a method for generating chlorine dioxide froma stable precursor by means of a transition metal. The chlorine dioxidethus generated can be used to disinfect solutions and devices,particularly contact lens solution and contact lenses.

BACKGROUND OF THE INVENTION

Chlorine dioxide has been found to act as a disinfecting agent. It mayhave application in disinfecting or sterilizing solutions and devices towhich they are applied. This technology has been found to beparticularly useful when applied to contact lens solutions and contactlenses.

Contact lenses should be periodically disinfected to protect thewearer's eyes from infection and to improve the wearer's comfort. It isoften desirable that lens disinfecting be accomplished quickly, e.g.,for the convenience of the wearer. However conventional fast-actingdisinfectants that are used with contact lenses have a high potential tocause eye irritation. Fast-acting disinfectants, such as hydrogenperoxide, cause a significant ocular irritation if placed directly inthe eye. Thus, when using such disinfectants, a thorough rinsing and/orneutralization step is required to remove substantially all traces ofthe disinfectant. Also, such disinfectants are often not stable and tendto lose their potency over time. A fast-acting, stable lens disinfectingsystem which is not as prone to cause eye irritation would clearly beadvantageous.

In addition to disinfecting contact lenses, they should also be cleanedof protein-based debris periodically. Such lens cleaning is done usingproteolytic enzymes. See for example, Karageozian U.S. Pat. No.3,910,296.

New compositions and methods for disinfecting devices, particularlycontact lenses, have been discovered. These compositions and methodsutilize the controlled formation of chlorine dioxide from a precursor bya transition metal, thought to be a catalytic process. The ability tocontrol the formation of chlorine dioxide allows one to effectively andefficiently ship and store the chlorine dioxide as an inactive precursorprior to use. Then, substantially on demand, the precursor is activatedor promoted to form or provide a disinfecting amount of chlorinedioxide.

An additional benefit of being able to control the formation or releaseof the chlorine dioxide is that it allows one to sequentially clean thelens using an enzymatic cleaner and then disinfect the lens in a onestep process. This is very convenient for the ultimate user, especiallya contact lens wearer, and provides the wearer with an easy and timeeffective way to maintain his or her lenses. The contact lens wearerexperiences more comfort and less irritation because his/her contactlenses are more apt to be clean and disinfected.

SUMMARY OF THE INVENTION

This invention relates in part to a method for generating chlorinedioxide in an aqueous medium, which method comprises buffering themedium to between pH 6-10, and exposing a stable chlorine dioxideprecursor to a transition metal for at least one minute.

In one aspect, this invention relates to a composition for generatingchlorine dioxide which comprises an aqueous medium, a compound capableof generating chlorine dioxide when exposed to a transition metal, and atransition metal which can catalytically generate chlorine dioxide fromsaid compound in an aqueous medium at a pH between 6-10.

Secondly, this invention relates to an aqueous composition having a pHbetween 6-10 for disinfecting a device which comprises a compoundcapable of generating chlorine dioxide when exposed to a transitionmetal in an aqueous medium and a transition metal which cancatalytically generate chlorine dioxide from said compound wherein aboutat least 0.1 ppm (0.1 mg per liter) of chlorine dioxide is generated.

Furthermore, there is disclosed a tablet comprising a compound capableof generating chlorine dioxide in an aqueous medium when exposed to atransition metal, and a transition metal which can catalyticallygenerates chlorine dioxide from said compound in an aqueous medium at apH between 6-10, and buffering agents capable of maintaining a pH ofbetween 6-10, wherein said tablet contains sufficient compound torelease about at least 0.1 ppm of chlorine dioxide.

Additionally, disclosed is a tablet for cleaning and disinfectingcontact lenses comprising a proteolytic enzyme in an amount between0.0003 and 0.5 Anson units, and a compound capable of generatingchlorine dioxide when exposed to a trasition metal in an aqueous mediumin an amount sufficient to generate about at least 0.1 ppm of chlorinedioxide, and optionally a transition metal, and buffering agents tomaintain the pH between 6-10.

In yet another aspect, there is disclosed a method for generatingchlorine dioxide in an aqueous medium, which method comprises bufferingthe medium to between pH 6-10, and exposing a chlorite compound or astabilized chlorine dioxide to a transition metal for at least oneminute.

DETAILED DESCRIPTION OF THE INVENTION

In its broadest aspect, the invention involves a method and compositionfor disinfecting a device of any sort. The device to be disinfected iscontacted with a composition including an aqueous medium and at leastone chlorine dioxide precursor. This contacting takes place in thepresence of at least one appropriate transition metal, present in anamount sufficient to facilitate or effect formation of a disinfectingamount of chlorine dioxide from the precursor compound. This contactingresults in the device being disinfected. The composition may includebuffer components in an amount effective to maintain the pH of themedium in a suitable or desirable pH range during formation of chlorinedioxide from the precursor. It has been found that certain buffers alsoprovide for increases in the rate and/or amount of chlorine dioxideformed from the precursor.

In another broad aspect of the invention, a formulation is providedwhich contains an enzyme for cleaning accretions and an appropriatemetal for activating or promoting release of chlorine dioxide from thestable precursor compound. This embodiment is most applicable to contactlenses. The lenses are exposed to one or more enzymes capable ofremoving debris from a contact lens in an amount effective tosubstantially remove debris from the lens and chlorine dioxide generatedby this activator/promoter and the stable chlorine dioxide source. Whatis envisioned is a one system where the enzyme and chlorine dioxide areplaced in a vial and effect their action without the operator having totake any further action. While the chlorine dioxide can be generatedcontemporaneously with treating the lenses with an enzyme, it ispreferred to conduct the cleaning step and disinfecting step in series.In other words, it is preferred to have one action be effected beforethe other action. For example the cleaning is effected by the enzymebefore the chlorine dioxide is generated, or vice-versa.

Any enzyme can be used in conjunction with this just described process.Proteolytic enzymes are preferred, but lipases or other enzymes whichhydrolyze carbohydrates, mucins or other debris which accumulates onsurfaces such as contact lenses may be used.

In one embodiment of the foregoing cleaning and disinfecting concept, anaqueous medium is provided which includes the chlorine dioxide precursorand the enzyme. The metal component may be present during the enzymecleaning in a substantially inactive form. If the enzyme, precursor andmetal component are all present during the enzyme cleaning, it ispreferred that either the precursor or the metal component be present ina substantially inactive form. This will reduce or eliminate anydeleterious or untoward effects the chlorine dioxide precursor orchlorine dioxide may have on enzymatic activity. For example, theprecursor or the transition metal component may be present in a delayedrelease form, in a tablet or pill, together with the enzyme. The enzymeis released substantially immediately on the tablet or pill beingsubmerged in the aqueous medium. The enzyme itself may be present in thetablet or pill, in a delayed release form. After submersion in theliquid medium, the enzyme is released first. After sufficient time foreffective enzymatic cleaning of the lens has elapsed, at least 15minutes or more, the precursor and the transition metal are released.This causes formation of chlorine dioxide and results in disinfectingthe enzymatically cleaned lens. This process can be reversed, that isthe chlorine dioxide can be generated, then after some discrete time,the enzyme is released into the solution for cleaning purposes.

As applied to lens cleaning and disinfecting, it is envisioned both willtake place in a single step in a single pot which does not have to beopened or acted on in order to effect both cleaning and disinfecting.The lens wearer does not need to closely monitor the process or changesolutions between the cleaning and disinfecting steps. Overall, thepresent invention is very easy and effective to use. This encouragescompliance with recommended lens care regimens.

The use of the chlorine dioxide generated by this invention isapplicable to disinfecting all types of contact lenses. Such lenses maybe made of any material or combination of materials and may have anysuitable configuration. For example, these solutions and compositionscan be used to disinfect lenses made from hydrogels ("soft" lenses),lenses made from polymethyl methacrylate (PMMA), the so called "hard"lenses and other non-hydrogel gas permeable lenses. Present day examplesor non-hydrogel gas permeable lens materials areoraganosiloxane-methyacrylate polymers (Polycon® lenses), fluorocarbonpolymers (Advent® lenses), cellulose acetate butyrate (CAB) materialsand silicone elastomer of various compositions. But this invention hasapplicability to all contact lenses regardless of their chemicalcomposition.

When the appropriate materials and amounts of materials are combined,sufficient chlorine dioxide will be generated to disinfect a givendevice or solution in a given period of time. Such materials and amountswill be those which in combination generate about at least 0.1 ppm ofchloride dioxide, more preferably about 0.2 ppm, most preferably 0.5ppm. The amount of chlorine dioxide, when present in solution, willdisinfect the solution or the device to which it is applied in about 1to 2 hours, or less. Higher amounts of chlorine dioxide will disinfectin a shorter period of time.

In general, the chlorine dioxide precursors referred to herein above arecompounds capable of generating, releasing or being converted to,chlorine dioxide when exposed to a transition metal. Preferred compoundsare those which produce chlorine dioxide in response to increasingacidity. Thus, in mildly acidic conditions, in particular at a pH ofless than about 6 and especially in the range of about 3 to 5, the rateof production of chlorine dioxide of these compounds is increasedrelative to a rate of chlorine dioxide production at neutral pH.

Among the preferred precursor compounds useful in the present inventionare chlorites and stabilized chlorine dioxide complexes. The term"stabilized chlorine dioxide" as used herein means, for example, one ormore chlorine dioxide-containing complexes disclosed in U.S. Pat. Nos.4,696,811 and 4,689,215 which are incorporated herein by reference.Chlorites include metal chlorite salts, particularly alkali metalchlorites. A specific example of a chlorite salt which is useful as achlorine dioxide precursor is sodium chlorite. Among the preferredstabilized chlorine dioxide complexes are carbonate and bicarbonatecomplexes. The exact chemical composition of many of these stabilizedchlorine dioxide precursors is not completely understood. Themanufacture or production of certain chlorine dioxide precursors isdescribed in McNicholas U.S. Pat. No. 3,278,447, which is herebyincorporated in its entirety by reference herein. An especially usefulstabilized chlorine dioxide is a product sold by Bio-Cide International,Inc. under the trademark PUROGENE®.

The chlorine dioxide precursor will be present in the aqueous medium ata predetermined concentration so as to provide a disinfecting amount ofchlorine dioxide in the presence of the promoting component. Preferably,the liquid medium has sufficient chlorine dioxide precursor so as tohave a potential of producing chlorine dioxide about 0.1 ppm.

In one embodiment, the chlorine dioxide precursor includes afunctionality selected from carbonate, borate, sulfate, phosphate, andmixtures thereof. Without intending to limit the scope of the presentinvention to any particular theory of operation, the inclusion of suchgroups in the chlorine dioxide precursor may correspond or be analogousto the effect of certain buffer components, as is discussed hereinafter.But the invention is fully operable without reference to a specificbuffer.

Any transition metal capable of effecting the release of chlorinedioxide from the precursor in an aqueous medium at a pH between 6-10, orpossibly higher, may be employed as a promoter in the present invention.The primary criteria for such transition metal is that it have theability to effect formation of a disinfecting amount of chlorine dioxidefrom the described chlorine dioxide precursors. Such metals should alsohave no substantial detrimental effect on the lens to be disinfected.

It is preferred that the metal component be present as a solid. Incertain embodiments, solid metals can be easily and convenientlyintroduced into or removed from the chlorine dioxideprecursor-containing liquid medium, as desired. Also a solid metalcomponent can be readily separated from the solution for repeated use indisinfecting lenses. The metal may be immobilized, or maintainedsubstantially stationary, relative to the solution.

The particular metals of interest herein are the transition metals andmixtures thereof, in particular from Group III metals, Group IV metals,Group V metals, Group VI metals, Group VII metals, Group VIII metals andmixtures thereof.

Because of their high degree of effectiveness, platinum group metals andmixture thereof, and especially platinum, are particularly useful. Theplatinum group metals include platinum, palladium, iridium, ruthenium,rhodium and osmium.

The metal or metals may be present in the metallic form and/or in acombined form as part of an organic or inorganic compound or complex.

The amount of metal needed to practice this invention is to be viewed interms of what quantity or surface area is useful to generate aparticular concentration of chlorine dioxide in a given time and inlight of the amount of precursor present in solution. It has beenobserved that the metal is not used up in the process of generatingchlorine dioxide. Thus it is assumed the metal acts as a catalyst toeffect formation of the chlorine dioxide. But the chemistry has not beeninvestigated other than to observe that the metal apparently is notconsumed in the process of creating chlorine dioxide.

Assuming the process is catalytic in nature, the amount of metal surfacearea exposed to the solution should be taken into consideration.Specific surface area data can be readily determined by simply exposinga chlorite salt of one concentration to various metals deposited ondifferent surface areas, then observing the rate of chlorine dioxideformation. From there, actual working parameters can be generated.Transition metals useful herein can also be dispersed in the aqueousmedium.

It is most convenient to plate the metals on some support device. Suchsupports are particularly useful in the metal includes one or moreplatinum group metals, which are quite expensive. The support may bechosen so as to provide surface area on which the promotion componentcan be placed.

Any suitable support material may be employed, and preferably issubstantially inert at the conditions employed in the present invention.Examples of support materials include polymeric materials (plastics),metals, aluminas, silicas, clays, ceramics and the like. The supportedpromotion component may have any suitable shape or configuration, suchas sheets, rods, extrudates, tablets, pills, irregular shapedparticulars, spheres, disks and the like. Any of a number ofconventional techniques can be employed to deposit the metal-containingcomponent on the support material. These techniques includeimpregnation, co-precipitation, ion-exchange, dipping, spraying, vacuumdepositions and the like.

The aqueous medium used is selected to have no substantial detrimentaleffect on the lens being treated and to allow and preferably to evenfacilitate the present lens treatment or treatments. If the devicesbeing disinfected are contact lenses, a particularly useful aqueousmedium is saline, for example, a saline solution conventionally used forwetting and storing contact lenses.

During the disinfecting contacting, it is preferred that the aqueousmedium have a pH in the range of about 6 to 10, but more preferablyabout 7.5. Such more preferred pH ranges are substantially consistentwith the normal physiological pH for humans. Thus, after disinfecting,the disinfected lens may be placed directly in the eye.

This invention may be practiced at a pH lower than 6. At that pH, andlower, chlorine dioxide is generated from chlorites and many stabilizedchlorine dioxides by virtue of the lower pH. In essence, the precursoris not stable for very long at these lower pHs at standard temperatureand pressure. So formulating a composition for use at some remote timesuch as is often encountered with consumer products where the shelf lifeof the product must be many months means this aspect of the inventionhas certain formulation limitations. But it has been found that atransition metal will increase the amount of chlorine dioxide generatedat lower pHs, as well as the rate at which it is generated. Thus,disinfecting in the presence of transition metal and chlorine dioxideprecursors under relatively highly acidic conditions is within the scopeof the present invention. If such highly acidic conditions are employed,a neutralization step may be useful to neutralize any acidic residuewhich may remain in or on the device. Neutralization can be easilyaccomplished by rinsing or soaking the disinfected device in a neutralor slightly basic saline solution.

The disinfecting contacting preferably occurs at room temperature, butmay be practiced at mildly elevated temperatures, up to 40° C. or thereabouts. This contacting preferably occurs for a time to substantiallycompletely disinfect the lens being treated. Such contacting times canbe in the range of about 5 minutes to about 2 hours or more depending onthe concentration of chlorine dioxide generated in the medium.

In order to ensure that the pH of the aqueous medium is maintainedwithin the desired range during the disinfecting procedure, the liquidaqueous medium may include at least one buffer component. Although anysuitable buffer component may be employed, it is preferred to selectsuch component so as not to substantially detrimentally affect thedesired formation of chlorine dioxide. It is preferred that the buffercomponent be inorganic.

Among the preferred buffer components are those which include phosphatefunctionalities, borate functionalities, carbonate functionalities andmixtures thereof. Particularly increased rates of chlorine dioxideformation are achieved when the buffer component includes phosphatefunctionalities, borate functionalities and mixtures thereof. Alkalimetal and alkaline earth metal salts of these buffer components areadvantageously used in the present invention.

In another embodiment, a composition is provided which includes anaqueous medium, at least one chlorine dioxide precursor capable ofgenerating chlorine dioxide when exposed to a transition metal, atransition metal and an enzyme. This composition or formula is usefulfor effecting a one-step cleaning and disinfecting of devices such ascontact lenses. By one-step it is meant that the cleaning anddisinfecting occurs in one vessel without changing solution. Preferably,this is accomplished sequentially. For example, one can provide theenzyme to the solution and then generate the chlorine dioxide or providethe enzyme to the same solution after disinfection has beenaccomplished. The liquid aqueous medium and chlorine dioxide precursorand promoter are described elsewhere herein.

The enzyme or enzymes used are capable of removing debris from a devicesuch as a contact lens. The amount of such enzyme or enzymes used(included in the present composition), protein, lipoproteins, lipids,mucins or saccharide should be effective to remove substantially all ofthe debris from a device such as a contact lens in a reasonable time,preferably in the range of about 5 minutes to 12 hours. The activeenzyme-containing liquid medium preferably contains sufficient enzyme toprovide between about 0.001 to about 5 Anson units of activity, morepreferably between about 0.01 to about 1 Anson units, per single lenstreatment. In weight/volume terms, since enzyme preparations are seldompure, it is expected that the enzyme source will be used in amountsbetween about 0.003 to 15% w/v of the final working solution. Theprecise amount will vary with the purity of the enzyme and will need tobe finally determined on a lot-by-lot basis.

The enzyme employed may be selected from enzymes which may be employedin the enzymatic cleaning of contact lenses. These include proteases,lipases, amylases, mucolytic enzymes or the like. Reference is made tothe compendium enzyme titles, "Enzyme Nomenclature," 1984, Ed. E. C.Webb, Academic Press, Inc., New York (1984). Any one or more of theseenzymes may be used in this invention as is appropriate and safe forremoving soils from devices. Where contact lenses are concerned, proteinand mucin buildup are two types of soils readily removed by enzymes.Hence, preferred formulations here include at least one protease and maycontain mucolytic enzymes as well. For example, many of the enzymesdisclosed in Huth et al. Reissue U.S. Pat. No. 32,672 are useful in thepresent invention.

It is preferred that the cleaning action of the enzyme or enzymes occurprior to the chlorine dioxide disinfecting of the lens. This is sobecause the chlorine dioxide may inactivate or destroy the enzyme beforecleaning has occurred. To effect this, the transition metal can be addedto or combined with the composition after the desired enzymatic cleaninghas occurred. But the compound from which the chlorine dioxide isgenerated may be present in the solution at the time enzymatic cleaningis desired, or may be effectively delayed in its introduction into thesolution either by adding a separate formulation or by encapsulatingthis compound in a delayed release formulation.

In another embodiment, the transition metal is included in thecomposition in a substantially non-promotional form, preferably in adelayed release form. For example, the enzyme and the chlorine dioxideprecursor and/or the metal may be present together in tablet or pill. Asthe tablet or pill is combined with the aqueous medium, the enzyme isreleased first and becomes available to remove debris from theto-be-cleaned lens. During this time, when the enzyme is cleaning thelens, the chlorine dioxide precursor and/or the metal-containingcomponent preferably both remain in the tablet or pill, effectively outof contact with the solution containing the enzyme during the cleaningphase of the lens treatment. After a period of time during which theenzyme effects a cleaned device, the chlorine dioxide precursor and themetal are introduced into the solution. This causes chlorine dioxide toform which, in turn, results in disinfecting the lens. Thus, a singletablet or pill can be used to both clean and disinfect the lens. It ispreferred that the tablet contain the enzyme, chlorine dioxide precursorand transition metal. In another useful embodiment, where no lenscleaning is desired, the tablet or pill contains just the chlorinedioxide precursor and transition metal. This tablet or pill, after beingintroduced into the solution, forms a lens disinfecting amount ofchlorine dioxide.

Although multi-layered (including core and coating layering) tablets orpills are preferred, the delayed release form of the present componentscan be present in any other suitable item or items, such as masses ofpowders, granules and the like. Delayed release technology is well knownin the art as exemplified by the text Controlled Drug Delivery, 2nd Ed.,Joseph R. Robinson and Vincent H. L. Lee, Eds., Marcel Dekker, Inc., NewYork, 1987.

Items which release their ingredients in a sequential, time delayedmanner are well known and can be produced using conventional technology.Therefore, a detailed description of such items and such productiontechnology is not presented here. However, such items are preferablydesigned to allow the enzyme or enzymes sufficient time to remove atleast a major amount, and more preferably substantially all, of thedebris from the lens. In other words, such components are preferablydesigned so that sufficient time elapses between release of the enzymeand formation of chlorine dioxide to allow the enzyme to perform itscleaning function. Such sufficient time is preferably in the range ofabout 1 minute to about 6 hours, more preferably about 15 minutes toabout 2 hour. Thirty to sixty minutes may also effectively clean anddisinfect lenses using these embodiments.

In one useful embodiment, the transition metal is incorporated into alens disinfecting system. This system comprises a chamber adapted andsized to hold the lens to be disinfected, and a solution containing atleast one chlorine dioxide precursor in an amount adequate upon exposureto the transition metal to produce sufficient chlorine dioxide todisinfect the lens. A support containing the transition metal is securedto the chamber and includes at least one solid transition metalcomponent in an amount to effect formation of sufficient chlorinedioxide from the chlorine dioxide precursor to disinfect lenses. Thetransition metal may be one or more of the transition metals describedabove.

The following examples illustrate certain aspects of the presentinvention.

EXAMPLE 1

This example illustrates the effect of stabilized chlorine dioxideconcentration on the production of chlorine dioxide.

A series of solutions was prepared using different concentrations of astabilized chlorine dioxide product, sold by Bio-Cide International,Inc. under the trademark Purogene®. The stabilized chlorine dioxideproduct included 2.0% by weight of potential (ultimate yield) chlorinedioxide and 0.085% by weight of sodium carbonate.

Each of these solutions was prepared as follows:

(1) 0.1% (W/V) of boric acid was dissolved in deionized water to providebuffering;

(2) a calculated amount of sodium chloride was added so that the finalsolution was isotonic;

(3) the pH of the solution was adjusted to 7.5%;

(4) the desired amount of the stabilized chlorine dioxide product wasadded; and

(5) the final volume of the solution was adjusted using deionized water.

Each of these solutions was tested as follows. A 10 ml. aliquot of thesolution was placed in a plastic container at ambient temperature andpressure. A plastic disc containing platinum as platinum oxide wasplaced in the solution. The concentration of chlorine dioxide wasmonitored as a function of time after the disc was placed in thecontainer.

Results of these tests are given in Table 1.

                  TABLE 1                                                         ______________________________________                                        Starting Conc. of                                                             precursor (PPM)                                                               Time       0.0    50     100  250  500  750  1000                             ______________________________________                                         0         0.0    0.00   0.00 0.00 0.00 0.00 0.00                              30        0.0    0.74   0.99 1.80 3.76 6.40 6.31                              60        0.0    0.94   1.61 5.11 6.11 8.19 10.79                             90        0.0    1.09   1.66 3.72 10.92                                                                              8.46 12.28                            120        0.0    0.90   1.81 4.06 12.08                                                                              11.80                                                                              12.78                            240        0.0    1.13   1.26 4.95 8.10 11.18                                                                              19.19                            480        0.0    1.00   1.28 4.08 5.17 10.23                                                                              13.78                            ______________________________________                                    

EXAMPLES 2 AND 3

Two series of solutions were prepared for testing. One set of solutionscontained 1000 ppm by weight of the stabilized chlorine dioxide asidentified in Example 1 and varying concentrations of sodium chlorideand borate buffer. The second set of solutions contained 1030 ppm. byweight of technical grade sodium chlorite and varying concentrations ofsodium chloride and borate buffer. This technical grade sodium chloritecontained: 80% by weight NaClO₂, 3% by weight NaC1, 5% by weight Na₂CO₃, 2% by weight NaClO₃.

Each of these solutions was tested in accordance with the procedureoutlined in Example 1. The chlorine dioxide concentration of eachaliquot was determined after 30 minutes exposure to the platinum disc.The pH was 7.5 for all solutions.

Results of these tests were as follows:

                  TABLE 2                                                         ______________________________________                                        EXAMPLE 2 - Stabilized Chlorine Dioxide Product (SCDP)                        SCDP,    NaCl    Borate Buffer,                                                                            ClO.sub.2                                                                              No Disc                                 ppm, by wt.                                                                            wt %    wt %        ppm, by wt.                                                                            Control                                 ______________________________________                                        1000     0.0     0.0         1.61     0.00                                    1000     0.7     0.0         1.41     0.00                                    1000     0.0     0.1         6.51     0.00                                    1000     0.7     0.1         6.31     0.00                                    ______________________________________                                        EXAMPLE 3 - Technical Grade Sodium Chlorite (TGSC)                            TGSC,    NaCl    Borate Buffer,                                                                            ClO.sub.2                                                                              No Disc                                 ppm, by wt.                                                                            wt %    wt %        ppm, by wt.                                                                            Control                                 ______________________________________                                        1030     0.0     0.0         1.28     0.00                                    1030     0.7     0.0         1.49     0.00                                    1030     0.0     0.1         7.29     0.00                                    1030     0.7     0.1         7.12     0.00                                    ______________________________________                                    

EXAMPLE 4

Another series of aqueous solutions was prepared using the sameconcentration of the stabilized chloride dioxide product as identifiedin Example 1 together with varying concentrations of boric acid. Each ofthese solutions was tested in accordance with the procedure outlined inExample 1. The chlorine dioxide concentration of each aliquot wasdetermined after 30 minutes exposure to the platinum disc.

Results of these tests were as follows:

                  TABLE 3                                                         ______________________________________                                        Boric Acid,   ClO.sub.2,  No Disc                                             wt. %         ppm, by wt %                                                                              Control                                             ______________________________________                                        0.00          2.10        0.00                                                0.025         4.36        0.00                                                0.050         5.36        0.00                                                0.100         6.32        0.00                                                0.150         7.22        0.00                                                0.200         7.50        0.00                                                0.250         9.62        0.00                                                0.300         10.30       0.00                                                0.400         11.20       0.00                                                0.500         11.23       0.00                                                0.600         11.29       0.00                                                0.800         11.38       0.00                                                ______________________________________                                    

These results show that chlorine dioxide production increased withincreasing boric acid concentrations up to a boric acid concentration ofabout 0.4% by weight. From 0.4% to 0.8% by weight of boric acid, theconcentration of chlorine dioxide remained substantially unchanged.

EXAMPLE 5

A further series of aqueous solutions was prepared with each solutionhaving the same concentration of the stabilized chlorine dioxide productas identified in Example 1 and substantially the same concentration ofsodium chloride. Each solution also included a substantially similarconcentration (on a molar basis) of a different buffer. A baselinesolution with no added buffer was also prepared. The pH of each solutionwas maintained at about 7.5 throughout the testing. Each of thesesolutions was tested in accordance with the procedure outlined inExample 1. The chlorine dioxide concentration of each solution wasdetermined after 30 minutes exposure to the platinum disc.

Results of these tests are given in Table 4.

                  TABLE 4                                                         ______________________________________                                                                     With Disc                                                Buffer Concen.                                                                            NaCl,    ClO.sub.2                                                                             Control                                  Buffer  molarity, wt %                                                                            wt %     ppm by wt                                                                             (No Disc)                                ______________________________________                                        none    --      --      0.70   1.41    0.00                                   TRIS    0.020   0.242   0.67   0.16    0.00                                   carbonate                                                                             0.020   0.212   0.60   5.35    0.00                                   boric acid                                                                            0.160   0.100   0.70   6.31    0.00                                   phosphate                                                                             0.020   0.276   0.63   6.80    0.00                                   ______________________________________                                    

The rate of chlorine dioxide generation from Purogene can be affected bythe particular buffer if one is used in maintaining the pH of thesesolutions. The use of the TRIS buffer appears to have a negative effecton CIO₂ release in this study.

Example 6

A series of aqueous solutions was prepared using 1000 ppm of thestabilized chlorine dioxide product set out in Example 1. Varyingamounts of sodium chloride were added to determine the effect of ionicstrength on chlorine dioxide production. Each of these solutions wastested in accordance with the procedure outline in Example 1. Thechlorine dioxide concentration of each aliquot was determined at 30minutes.

Results of these tests are given in Table 5.

                  TABLE 5                                                         ______________________________________                                        NaCl,        ClO.sub.2   No Disc                                              wt %         ppm, by wt  Control                                              ______________________________________                                        0.0          7.62        0.00                                                 0.1          6.99        0.00                                                 0.4          6.96        0.00                                                 0.7          7.14        0.00                                                 1.0          7.06        0.00                                                 1.3          6.88        0.00                                                 1.3          6.80        0.00                                                 ______________________________________                                    

These results indicate that the ionic strength of the solution hadlittle effect on the production of chlorine dioxide. As sodium chloridecontent was increased from 0.0% to 0.1% by weight, there was a 9% dropin chlorine dioxide production. Further increases in ionic strength didnot substantially affect chlorine dioxide production.

EXAMPLE 7

Three aqueous solutions containing the same concentration, 50 ppm. byweight, of the stabilized chlorine dioxide product identified in Example1 were prepared. The solutions also included 0.1% by weight of boricacid and 0.85% by weight of sodium chloride. Each of these solutions hada different pH and was tested in accordance with the procedure outlinedin Example 1. The chlorine dioxide concentration of each aliquot wasdetermined after 30 minutes exposure to the platinum-containing disc.

Results of these tests are given in Table 6.

                  TABLE 6                                                         ______________________________________                                                   No Disc  ClO.sub.2 Concentration,                                  pH         (ClO.sub.2)                                                                            ppm., by wt.                                              ______________________________________                                        7.9        0.00     1.10                                                      7.5        0.00     2.35                                                      6.8        0.00     3.42                                                      ______________________________________                                    

There was approximately three (3) times as much chlorine dioxideproduced at pH 6.8 as at pH 7.9.

EXAMPLE 8

Two solutions containing 50 ppm of the stabilized chlorine dioxideproduct identified in Example 1 were prepared. One solution had a pH of6.5 and the other solution had a pH of 6.0. Each of these solutions wasmonitored for chlorine dioxide concentration both with and without theplatinum-containing disc described in Example 1.

Results of these tests are set out in Table 7

                  TABLE 7                                                         ______________________________________                                                 pH - 6.0            pH - 6.5                                                  ClO.sub.2 Concentration,                                                                          ClO.sub.2 Concentration,                         Time,    ppm., by wt.        ppm., by wt.                                     Minutes  No Disc  Disc       No Disc                                                                              Disc                                      ______________________________________                                         0       0.944    0.944      0.023  0.023                                     30       0.601    2.547      0.094  1.105                                     90       0.338    2.523      0.039  1.170                                     120      0.318    1.984      0.258  1.227                                     ______________________________________                                    

These results indicate that platinum oxide increases the production ofchlorine dioxide even as the pH is lowered. Thus, it may be advantageousto contact the lens to be disinfected with the chlorine dioxideprecursor in the presence of a metal-containing component at a pH lowerthan the normal human physiological range. This treatment may involve asubsequent neutralization step in order to ready the disinfected lensfor wear.

EXAMPLE 9

Various platinum discs were selected for testing. Each of the discs hada different geometric surface area. The solution used in this testingincluded 200 ppm by weight of the stabilized chlorine dioxide productidentified in Example 1. Each of these discs was tested in accordancewith the procedure outlined in Example 1. The chlorine dioxideconcentration of each aliquot was determined after 30 minutes exposureto the platinum disc.

Table 8 sets out these results.

                  TABLE 8                                                         ______________________________________                                        Surface Area  ClO.sub.2 Concentration,                                        cm.sup.2      ppm, by wt.                                                     ______________________________________                                        2.50          0.32                                                            3.50          0.63                                                            5.30          0.72                                                            5.57          0.70                                                            5.73          0.63                                                            6.00          1.04                                                            11.30         1.83                                                            11.30         2.14                                                            11.30         1.50                                                            16.87         2.62                                                            22.60         2.73                                                            ______________________________________                                    

These results demonstrate that as the geometric surface area of the discincreased past 11.3 cm², the production of chlorine dioxide continued toincrease, but at a slower, non-linear rate.

EXAMPLE 10

Aluminum pellets coated with ruthenium oxide and having a surface areaof about 7.9 cm² were selected for testing. These pellets were exposedto an aqueous solution of 200 ppm of the stabilized chlorine dioxideproduct for 30 minutes using the same container as in Example 1. Theconcentration of chlorine dioxide was monitored.

The average amount of chlorine dioxide produced per cm² ofruthenium-containing pellet surface area was about 0.080 ppm. Thecomparable average amount of chlorine dioxide produced per cm² ofplatinum-containing disc surface area was about 0.146 ppm. The controlsolution with no disc produced 0.00 ppm C10₂. Although the rutheniumoxide pellets were not as effective as the platinum oxide disc, it isbelieved that ruthenium oxide pellets are useful in the presentinvention, particularly if higher surface area pellets are employed andthe amount of chlorine dioxide precursor is increased.

EXAMPLE 11

A solution containing deionized water, 0.85% (w/v) of sodium chloride,0.10% (w/v) of boric acid, and 50 pp. w/v of the stabilized chlorinedioxide product identified in Example 1 was prepared. One portion ofthis solution was buffered to a pH 7.9, while the other portion wasbuffered to a pH of 6.8. Varying amounts of tartaric acid was added todifferent aliquots of each of these portions. The aliquots were thentested, following the standard procedure, to determine the D-value withrespect to various microorganisms. The D-value is defined as the lengthof time required to reduce the microbial burden or load by one log unit.

Results are given in Table 9.

                  TABLE 9                                                         ______________________________________                                        pH = 6.8                                                                      Tartaric Acid, ppm.                                                                        30      40      50    60    70                                   Free Chlorine                                                                              10.74   17.08   37.94 25.38 32.47                                Dioxide, ppm                                                                  Microorganism                                                                              Extrapolated D-value at 23° C., min.                      S. marcescens                                                                              <0.84   <0.84   <0.84 <0.84 <0.84                                S. aureus    <0.87   <0.87   <0.87 <0.87 <0.87                                P. aeruginosa                                                                              <0.85   <0.85   <0.85 <0.85 <0.85                                A. fumigatus <0.83   <0.83   <0.83 <0.83 <0.83                                pH = 7.9                                                                      Tartaric Acid, ppm.                                                                        30      40      50    60    70                                   Free Chlorine                                                                              0.03    0.11    0.05  0.15  0.23                                 Dioxide, ppm.                                                                 Microorganism                                                                              Extrapolated D-value at 23° C., min.                      S. marcescens                                                                              5.13    <0.85   2.56  <0.85 2.56                                 S. aureus    10.17   2.54    2.54  12.24 2.54                                 P. aeruginosa                                                                              19.48   <0.87   2.6   <0.87 <0.87                                A. fumigatus 109     109     150   162.2 70.6                                 ______________________________________                                    

These results indicate that chlorine dioxide in an aqueous solution iseffective to disinfect contact lenses. Thus, these results demonstratethat sufficient chlorine dioxide can be provided in a liquid medium toreduce the microbial burden or load by one log order in a period of timegenerally deemed acceptable for disinfecting contact lenses.

EXAMPLE 12

This example illustrates a lens cleaning and disinfecting embodiment ofthe present invention.

A protein-based debris laden hydrogel contact lens is placed in aplastic container. A quantity of a saline solution containing 500 ppm byweight of the stabilized chlorine dioxide product identified in Example1 and 0.3% by weight of boric acid is added to the container. The pH ofthis solution is about 7.5.

A layered, delayed release tablet is dropped into the solution in thecontainer. The center core of this tablet is a plastic disc whichincludes a platinum-containing coating. The outer layer of the tabletincludes a quantity of a proteolytic enzyme. The layer between theenzyme-containing layer and the platinum coated disc is structured anddesigned to completely dissolve or destruct in 30 minutes after beingexposed to the solution in the container.

Upon being dropped into the solution, the enzyme in the outer layer ofthe tablet is released and begins to break down the protein-based debrison the lens. In 30 minutes, substantially all of the protein-baseddebris is removed from the lens, and the platinized disc is exposed tothe solution. This exposure results in the production of a disinfectingamount of chlorine dioxide which acts to disinfect the cleaned lens.Throughout this procedure the pH of the solution remains in thephysiological range.

Six hours after the tablet is dropped into the solution, the cleaned anddisinfected lens is removed from the solution. After a light salinerinse the lens is ready to be placed in the lens wearer's eye.

This cleaning/disinfecting procedure requires only one step as opposedto conventional separate cleaning and disinfecting steps with the needfor human intervention between the steps. Thus, the present system isvery convenient to use and reduces the amount of time the wearer mustactively spend to clean and disinfect his/her lenses.

While this invention has been described with respect to various specificexamples and embodiments, it is to be understood that the invention isnot limited thereto.

What is claimed is:
 1. A tablet capable of generating chlorine dioxidein an aqueous medium comprising a chlorine dioxide precursor capable ofgenerating chlorine dioxide when exposed to a transition metal, atransition metal component effective to promote the generation ofchlorine dioxide from said chlorine dioxide precursor in an aqueousmedium at a pH in the range of about 6 to about 10, and a bufferingcomponent in an amount effective to maintain the pH of the aqueousmedium in which said tablet is released in the range of about 6 to about10, said buffering component being effective to increase the rate ofchlorine dioxide generation from said chlorine dioxide precursorrelative to a similar tablet without said buffering component, whereinsaid tablet contains sufficient chlorine dioxide precursor to produce atleast about 0.2 ppm of chlorine dioxide in the aqueous medium in whichsaid tablet is released.
 2. The tablet of claim 1 where said chlorinedioxide precursor is a chlorite salt and said transition metal componentcomprises platinum or ruthenium.
 3. The tablet of claim 1 which furthercomprises an outer layer comprising a proteolytic enzyme in an amount inthe range of about 0.001 to about 5 Anson units, said chlorine dioxideprecursor, said transition metal component and said buffering componentbeing located in a core, and a delayed release barrier located betweenthe outer layer and the core which delays the release of the core for atleast about 15 minutes.
 4. The tablet of claim 1 wherein said chlorinedioxide precursor is selected from the group consisting of chloritesalts and mixtures thereof.
 5. The tablet of claim 1 wherein saidtransition metal component comprises a metal selected from the groupconsisting of platinum, palladium and ruthenium.
 6. The tablet of claim1 wherein said buffering component includes at least one functionalityselected from the group consisting of phosphate functionalities, boratefunctionalities, carbonate functionalities and mixtures thereof.
 7. Atablet for cleaning and disinfecting contact lenses comprising an outerlayer comprising a proteolytic enzyme in an amount in the range of about0.001 to about 5 Anson units, and an inner core encapsulated in adelayed release component which acts to delay the release of the innercore for at least about fifteen minutes after the tablet is placed in anaqueous medium, wherein the inner core comprises a chlorine dioxideprecursor capable of generating chlorine dioxide when exposed to atransition metal in an amount sufficient to generate at least 0.1 ppm ofchlorine dioxide, a transition metal component, and a bufferingcomponent effective to maintain the pH of the aqueous medium in whichthe tablet is released in the range of about 6 to about 10, saidbuffering component being effective to increase the rate of chlorinedioxide generation from said chlorine dioxide precursor relative to asimilar tablet without said buffering component.
 8. The tablet of claim7 wherein said chlorine dioxide precursor is selected from the groupconsisting of chlorite salts and mixtures thereof.
 9. The tablet ofclaim 7 wherein said transition metal component comprises a metalselected from the group consisting of platinum, palladium and ruthenium.10. The tablet of claim 7 wherein said buffering component includes atleast one functionality selected from the group consisting of phosphatefunctionalities, borate functionalities, carbonate functionalites andmixtures thereof.